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1.
Sci Rep ; 14(1): 20901, 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39245776

RESUMEN

Nowadays, human activities intensified the combined pollution of fluoride and lead in acidic tea garden soil. The key to eliminating this combined pollution is to immobilize pollutants simultaneously, thus preventing their migration from tea garden soil to tea trees. In this paper, the natural product bayberry tannin was employed as raw material to fabricate functional materials (TF-Zr) for simultaneous adsorption of fluorine (F) and lead (Pb) in water and soil by the reactivity of tannin with Pb2+ and the affinity of Zr with F. SEM-Mapping, EDS, FT-IR, XPS were utilized to probe the immobilization mechanisms. The results showed that TF-Zr could simultaneously and efficiently adsorb F- and Pb2+ from water with the adsorption capacity of 5.02 mg/g (Pb) and 4.55 mg/g (F). The adsorption processes were both in accordance with the proposed secondary kinetic adsorption model. Besides, the presence of F- promoted the adsorption of Pb2+ by TF-Zr. The materials were applied into tea garden soil to explore its effect on the variation of F and Pb forms in the soil. It was found that the proportion of water-soluble fluorine, exchangeable fluorine and exchangeable lead in the tea garden soil decreased significantly, while the proportion of residual fluorine and lead increased evidently, illustrating TF-Zr possessed eximious fixation effect on the highly reactive fluorine and lead in the soil and facilitated their conversion to the more stable residue state. Therefore, TF-Zr can be used for the efficient and simultaneous immobilization of fluorine and lead in water and tea garden soil.

2.
BMC Musculoskelet Disord ; 25(1): 702, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227803

RESUMEN

BACKGROUND: The effect of fat infiltration in the paraspinal muscles on cervical degenerative disease has been confirmed by multiple studies. However, little is known about fat infiltration in the paraspinal extensors in patients with acute cervical spinal cord injury (SCI). This study aimed to investigate the difference in paraspinal extensor fatty infiltration between patients with acute cervical SCI and healthy controls, and to further explore the protective role of the paravertebral extensor muscles in patients with cervical SCI. METHODS: A total of 50 patients with acute cervical SCI admitted to the emergency department from January 2019 to November 2023 were retrospectively analyzed, including 26 males and 24 females, with an average age of 59.60 ± 10.81 years. A control group of 50 healthy middle-aged and elderly individuals was also included, comprising 28 males and 22 females, with an average age of 55.00 ± 8.21 years. Cervical spine magnetic resonance imaging (MRI) was used to measure the cross-sectional areas of the superficial and deep cervical extensor muscles, the corresponding vertebral body cross-sectional areas, and the fat area within the superficial and deep extensor muscle groups using Image J software. Differences between the two groups were compared, and the cervical SCI patients were further analyzed based on the severity of the spinal cord injury and gender differences. RESULTS: The deep fatty infiltration ratio (DFIR) and superficial fatty infiltration ratio (SFIR) at C4-C7 in the cervical SCI group were significantly higher than those in the control group (P < 0.001). The cross-sectional area of the functional deep extensor area (FDEA) relative to the vertebral body area (VBA) and the cross-sectional area of the functional superficial extensor area (FSEA) relative to the VBA at the C5 and C6 levels in the cervical SCI group were significantly lower than those in the control group (P < 0.001, P < 0.001, P = 0.034, P = 0.004 respectively). Among the cervical SCI patients, the cross-sectional areas of the deep extensor area (DEA) and the superficial extensor area (SEA) in males were significantly higher than those in females (P < 0.001). At the C6 and C7 levels, the FDEA/VBA and FSEA/VBA ratios in the male group were higher than those in the female group (P = 0.009, P = 0.022, P = 0.019, P = 0.005, respectively). CONCLUSION: Patients with acute cervical SCI exhibit significantly higher fatty infiltration and a greater degree of paravertebral extensor muscle degeneration compared to healthy controls. This finding underscores the importance of the paravertebral extensor muscles in the context of cervical SCI and may guide future therapeutic strategies.


Asunto(s)
Tejido Adiposo , Vértebras Cervicales , Imagen por Resonancia Magnética , Músculos Paraespinales , Traumatismos de la Médula Espinal , Humanos , Masculino , Femenino , Traumatismos de la Médula Espinal/diagnóstico por imagen , Traumatismos de la Médula Espinal/patología , Estudios Retrospectivos , Persona de Mediana Edad , Músculos Paraespinales/diagnóstico por imagen , Músculos Paraespinales/patología , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/patología , Anciano , Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo/patología , Adulto , Estudios de Casos y Controles
3.
Materials (Basel) ; 17(15)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39124321

RESUMEN

Ultrafast laser technology has moved from ultrafast to ultra-strong due to the development of chirped pulse amplification technology. Ultrafast laser technology, such as femtosecond lasers and picosecond lasers, has quickly become a flexible tool for processing brittle and hard materials and complex micro-components, which are widely used in and developed for medical, aerospace, semiconductor applications and so on. However, the mechanisms of the interaction between an ultrafast laser and brittle and hard materials are still unclear. Meanwhile, the ultrafast laser processing of these materials is still a challenge. Additionally, highly efficient and high-precision manufacturing using ultrafast lasers needs to be developed. This review is focused on the common challenges and current status of the ultrafast laser processing of brittle and hard materials, such as nickel-based superalloys, thermal barrier ceramics, diamond, silicon dioxide, and silicon carbide composites. Firstly, different materials are distinguished according to their bandgap width, thermal conductivity and other characteristics in order to reveal the absorption mechanism of the laser energy during the ultrafast laser processing of brittle and hard materials. Secondly, the mechanism of laser energy transfer and transformation is investigated by analyzing the interaction between the photons and the electrons and ions in laser-induced plasma, as well as the interaction with the continuum of the materials. Thirdly, the relationship between key parameters and ultrafast laser processing quality is discussed. Finally, the methods for achieving highly efficient and high-precision manufacturing of complex three-dimensional micro-components are explored in detail.

4.
Cell Rep ; 43(8): 114616, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39128004

RESUMEN

Although aberrant activation of the KRAS and PI3K pathway alongside TP53 mutations account for frequent aberrations in human gastric cancers, neither the sequence nor the individual contributions of these mutations have been clarified. Here, we establish an allelic series of mice to afford conditional expression in the glandular epithelium of KrasG12D;Pik3caH1047R or Trp53R172H and/or ablation of Pten or Trp53. We find that KrasG12D;Pik3caH1047R is sufficient to induce adenomas and that lesions progress to carcinoma when also harboring Pten deletions. An additional challenge with either Trp53 loss- or gain-of-function alleles further accelerated tumor progression and triggered metastatic disease. While tumor-intrinsic STAT3 signaling in response to gp130 family cytokines remained as a gatekeeper for all stages of tumor development, metastatic progression required a mutant Trp53-induced interleukin (IL)-11 to IL-6 dependency switch. Consistent with the poorer survival of patients with high IL-6 expression, we identify IL-6/STAT3 signaling as a therapeutic vulnerability for TP53-mutant gastric cancer.


Asunto(s)
Progresión de la Enfermedad , Interleucina-6 , Factor de Transcripción STAT3 , Neoplasias Gástricas , Proteína p53 Supresora de Tumor , Animales , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Interleucina-6/metabolismo , Interleucina-6/genética , Ratones , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Mutación/genética , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Humanos , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Interleucina-11/metabolismo , Interleucina-11/genética
5.
Mol Cell Biochem ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38985252

RESUMEN

Cardiovascular disease (CVD) stands as a predominant global cause of morbidity and mortality, necessitating effective and cost-efficient therapies for cardiovascular risk reduction. Mitochondrial coupling factor 6 (CF6), identified as a novel proatherogenic peptide, emerges as a significant risk factor in endothelial dysfunction development, correlating with CVD severity. CF6 expression can be heightened by CVD risk factors like mechanical force, hypoxia, or high glucose stimuli through the NF-κB pathway. Many studies have explored the CF6-CVD relationship, revealing elevated plasma CF6 levels in essential hypertension, atherosclerotic cardiovascular disease (ASCVD), stroke, and preeclampsia patients. CF6 acts as a vasoactive and proatherogenic peptide in CVD, inducing intracellular acidosis in vascular endothelial cells, inhibiting nitric oxide (NO) and prostacyclin generation, increasing blood pressure, and producing proatherogenic molecules, significantly contributing to CVD development. CF6 induces an imbalance in endothelium-dependent factors, including NO, prostacyclin, and asymmetric dimethylarginine (ADMA), promoting vasoconstriction, vascular remodeling, thrombosis, and insulin resistance, possibly via C-src Ca2+ and PRMT-1/DDAH-2-ADMA-NO pathways. This review offers a comprehensive exploration of CF6 in the context of CVD, providing mechanistic insights into its role in processes impacting CVD, with a focus on CF6 functions, intracellular signaling, and regulatory mechanisms in vascular endothelial cells.

6.
Genet Test Mol Biomarkers ; 28(7): 281-288, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38949978

RESUMEN

Objective: To investigate the association between ACTN4 gene mutation and primary nephrotic syndrome (PNS) in children in Guangxi Autonomous Region, China. Methods: The high-throughput sequencing technology was used to sequence ACTN4 gene in 155 children with PNS in Guangxi Autonomous Region in China, with 98 healthy children serving as controls. Twenty-three exon-specific capture probes targeting ACTN4 were designed and used to hybridize with the genomic DNA library. The targeted genomic region DNA fragments were enriched and sequenced. The protein levels of ACTN4 in both case and control groups were quantified using ELISA method. Results: Bioinformatics analysis revealed five unique ACTN4 mutations exclusively in patients with PNS, including c.1516G>A (p.G506S) on one exon in 2 patients, c.1442 + 10G>A at the splice site in 1 patient, c.1649A>G (p.D550G) on exon in 1 patient, c.2191-4G>A at the cleavage site in 2 patients, and c.2315C>T (p.A772V) on one exon in 1 patient. The c.1649A>G (p.D550G) and c.2315C>T (p.A772V) were identified from the same patient. Notably, c.1649A>G (p.D550G) represents a novel mutation in ACTN4. In addition, three other ACTN4 polymorphisms occurred in both case and control groups, including c.162 + 6C>T (1 patient in case group and 2 patients in control group), c.572 + 11G>A (1 patient in case group and 2 patients in control group), and c.2191-5C>T (4 patients in the case group and 3 patients in control group). The serum ACTN4 concentration in the case group was markedly higher, averaging 544.7 ng/mL (range: 264.6-952.6 ng/mL), compared with 241.20 ng/mL (range: 110.75-542.35 ng/mL) in the control group. Conclusion: Five ACTN4 polymorphisms were identified among children with PNS in Guangxi Autonomous Region, China, including the novel mutation c.1649A>G. The lower serum levels of α-actinin-4 in the case group suggest that this protein might play a protective role in PNS.


Asunto(s)
Actinina , Síndrome Nefrótico , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Actinina/genética , Estudios de Casos y Controles , China/epidemiología , Exones/genética , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mutación , Síndrome Nefrótico/genética , Pueblos del Este de Asia/genética
7.
Imeta ; 3(1): e162, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38868512

RESUMEN

Regulation on denitrifying microbiomes is crucial for sustainable industrial biotechnology and ecological nitrogen cycling. The holistic genetic profiles of microbiomes can be provided by meta-omics. However, precise decryption and further applications of highly complex microbiomes and corresponding meta-omics data sets remain great challenges. Here, we combined optogenetics and geometric deep learning to form a discover-model-learn-advance (DMLA) cycle for denitrification microbiome encryption and regulation. Graph neural networks (GNNs) exhibited superior performance in integrating biological knowledge and identifying coexpression gene panels, which could be utilized to predict unknown phenotypes, elucidate molecular biology mechanisms, and advance biotechnologies. Through the DMLA cycle, we discovered the wavelength-divergent secretion system and nitrate-superoxide coregulation, realizing increasing extracellular protein production by 83.8% and facilitating nitrate removal with 99.9% enhancement. Our study showcased the potential of GNNs-empowered optogenetic approaches for regulating denitrification and accelerating the mechanistic discovery of microbiomes for in-depth research and versatile applications.

9.
Dev Cell ; 59(15): 1988-2004.e11, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38781975

RESUMEN

The transcription factor EHF is highly expressed in the lactating mammary gland, but its role in mammary development and tumorigenesis is not fully understood. Utilizing a mouse model of Ehf deletion, herein, we demonstrate that loss of Ehf impairs mammary lobuloalveolar differentiation at late pregnancy, indicated by significantly reduced levels of milk genes and milk lipids, fewer differentiated alveolar cells, and an accumulation of alveolar progenitor cells. Further, deletion of Ehf increased proliferative capacity and attenuated prolactin-induced alveolar differentiation in mammary organoids. Ehf deletion also increased tumor incidence in the MMTV-PyMT mammary tumor model and increased the proliferative capacity of mammary tumor organoids, while low EHF expression was associated with higher tumor grade and poorer outcome in luminal A and basal human breast cancers. Collectively, these findings establish EHF as a non-redundant regulator of mammary alveolar differentiation and a putative suppressor of mammary tumorigenesis.


Asunto(s)
Neoplasias de la Mama , Diferenciación Celular , Glándulas Mamarias Animales , Animales , Femenino , Humanos , Ratones , Embarazo , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Células Epiteliales Alveolares/citología , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Carcinogénesis/patología , Carcinogénesis/metabolismo , Carcinogénesis/genética , Linaje de la Célula , Proliferación Celular , Lactancia , Glándulas Mamarias Animales/patología , Glándulas Mamarias Animales/metabolismo , Glándulas Mamarias Animales/crecimiento & desarrollo , Glándulas Mamarias Animales/citología , Factores de Transcripción/metabolismo , Factores de Transcripción/genética
10.
Environ Mol Mutagen ; 65(3-4): 116-120, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38651401

RESUMEN

The Ames test is required by regulatory agencies worldwide for assessing the mutagenic and carcinogenic potential of chemical compounds. This test uses several strains of bacteria to evaluate mutation induction: positive results in the assay are predictive of rodent carcinogenicity. As an initial step to understanding how well the assay may detect mutagens present as constituents of complex mixtures such as botanical extracts, a cross-sector working group examined the within-laboratory reproducibility of the Ames test using the extensive, publicly available National Toxicology Program (NTP) Ames test database comprising more than 3000 distinct test articles, most of which are individual chemicals. This study focused primarily on NTP tests conducted using the standard Organization for Economic Co-operation and Development Test Guideline 471 preincubation test protocol with 10% rat liver S9 for metabolic activation, although 30% rat S9 and 10 and 30% hamster liver S9 were also evaluated. The reproducibility of initial negative responses in all strains with and without 10% S9, was quite high, ranging from 95% to 99% with few exceptions. The within-laboratory reproducibility of initial positive responses for strains TA98 and TA100 with and without 10% rat liver S9 was ≥90%. Similar results were seen with hamster S9. As expected, the reproducibility of initial equivocal responses was lower, <50%. These results will provide context for determining the optimal design of recommended test protocols for use in screening both individual chemicals and complex mixtures, including botanicals.


Asunto(s)
Pruebas de Mutagenicidad , Animales , Pruebas de Mutagenicidad/métodos , Reproducibilidad de los Resultados , Ratas , Mutágenos/toxicidad , Cricetinae , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Hígado/efectos de los fármacos , Laboratorios/normas
11.
Open Life Sci ; 19(1): 20220839, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38585629

RESUMEN

Gastric mucosal samples were procured and underwent the sequencing of 16S ribosomal RNA (16S rRNA) via Illumina high-throughput sequencing technology to explore the impact of Helicobacter pylori (H. pylori) infection on the composition of gastric flora in chronic gastritis (CG) patients. In the results, the operational taxonomic unit (OTU) analysis revealed an overlap of 5706 OTUs shared between the two groups. The top 5 abundance ranking (TOP5) phyla comprised Bacteroidetes, Proteobacteria, Firmicutes, Actinobacteria, and Epsilonbacteraeota, while the TOP5 genus was Lachnospiraceae_NK4A136_group, Helicobacter, Bacteroides, Klebsiella, and Pseudomonas. In the metabolic pathways at the Kyoto Encyclopedia of Genes and Genomes (KEGG)_L3 level, conspicuous variations across seven functions were observed between the H. pylori-positive (HP_Pos) and H. pylori-negative (HP_Neg) groups. Subsequently, functional gene enrichment in KEGG pathways was further validated through animal experimentation. In contrast to the mice in the HP_Neg group, those infected with H. pylori manifested an infiltration of inflammatory cells, an augmentation in gastric acid secretion, and conspicuously elevated scores regarding gastric activity, along with heightened levels of malondialdehyde. In conclusion, CG patients infected with H. pylori displayed a disorder in gastric flora, furnishing a theoretical basis for the prophylaxis of H. pylori infection and its associated pathogenic ramifications.

12.
Microbiol Res ; 283: 127696, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38518453

RESUMEN

Boreal forests commonly suffer from nutrient deficiency due to restricted biological activity and decomposition. Biochar has been used as a promising strategy to improve soil quality, yet its impacts on forest soil microbes, particularly in cold environment, remains poorly understood. In this study, we investigated the effects of biochar, produced at different pyrolysis temperatures (500 °C and 650 °C) and applied at different amounts (0.5 kg·m-2 and 1.0 kg·m-2), on soil property, soil enzyme activity, and fungal community dynamics in a boreal forest over a span of two to four years. Our results showed that, four-year post-application of biochar produced at 650 °C and applied at 1.0 kg·m-2, significantly increased the relative abundance of Mortierellomycota and enhanced fungal species richness, α-diversity and evenness compared to the control (CK) (P < 0.05). Notably, the abundance of Phialocephala fortinii increased with the application of biochar produced at 500 °C and applied at 0.5 kg·m-2, exhibiting a positively correlation with the carbon cycling-related enzyme ß-cellobiosidase. Functionally, distinct fungal gene structures were formed between different biochar pyrolysis temperatures, and between application amounts in four-year post-biochar application (P < 0.05). Additionally, correlation analyses revealed the significance of the duration post-biochar application on the soil properties, soil extracellular enzymes, soil fungal dominant phyla, fungal community and gene structures (P < 0.01). The interaction between biochar pyrolysis temperature and application amount significantly influenced fungal α-diversity (P < 0.01). Overall, these findings provide theoretical insights and practical application for biochar as soil amendment in boreal forest ecosystems.


Asunto(s)
Carbón Orgánico , Micobioma , Resiliencia Psicológica , Suelo/química , Taiga , Ecosistema , Microbiología del Suelo
13.
Bioresour Technol ; 398: 130529, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38437969

RESUMEN

The process of biological fermentation is often accompanied by the release of CO2, resulting in low yield and environmental pollution. Refixing CO2 to the product synthesis pathway is an attractive approach to improve the product yield. Cadaverine is an important diamine used for the synthesis of bio-based polyurethane or polyamide. Here, aiming to increase its final production, a RuBisCO-based shunt consisting of the ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) and phosphoribulate kinase (PRK) was expressed in cadaverine-producing E. coli. This shunt was calculated capable of increasing the maximum theoretical cadaverine yield based on flux model analysis. When a functional RuBisCO-based shunt was established and optimized in E. coli, the cadaverine production and yield of the final engineered strain reached the highest level, which were 84.1 g/L and 0.37 g/g Glucose, respectively. Thus, the design of in situ CO2 fixation provides a green and efficient industrial production process.


Asunto(s)
Escherichia coli , Ribulosa-Bifosfato Carboxilasa , Ribulosa-Bifosfato Carboxilasa/metabolismo , Cadaverina/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Dióxido de Carbono/metabolismo , Fermentación
14.
Cell Rep ; 43(3): 113831, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38401121

RESUMEN

Cancer immunotherapies have demonstrated remarkable success; however, the majority of patients do not respond or develop resistance. Here, we conduct epigenetic gene-targeted CRISPR-Cas9 screens to identify epigenomic factors that limit CD8+ T cell-mediated anti-tumor immunity. We identify that PRMT1 suppresses interferon gamma (Ifnγ)-induced MHC-I expression, thus dampening CD8+ T cell-mediated killing. Indeed, PRMT1 knockout or pharmacological targeting of type I PRMT with the clinical inhibitor GSK3368715 enhances Ifnγ-induced MHC-I expression through elevated STAT1 expression and activation, while re-introduction of PRMT1 in PRMT1-deficient cells reverses this effect. Importantly, loss of PRMT1 enhances the efficacy of anti-PD-1 immunotherapy, and The Cancer Genome Atlas analysis reveals that PRMT1 expression in human melanoma is inversely correlated with expression of human leukocyte antigen molecules, infiltration of CD8+ T cells, and overall survival. Taken together, we identify PRMT1 as a negative regulator of anti-tumor immunity, unveiling clinical type I PRMT inhibitors as immunotherapeutic agents or as adjuncts to existing immunotherapies.


Asunto(s)
Linfocitos T CD8-positivos , Melanoma , Humanos , Linfocitos T CD8-positivos/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Antígenos de Histocompatibilidad Clase I/genética , Inmunidad Celular , Interferón gamma/metabolismo , Melanoma/patología , Proteínas Represoras/genética , Proteínas Represoras/metabolismo
15.
PLoS One ; 19(2): e0298348, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38363740

RESUMEN

With the continuous advancement of technology, automated vehicle technology is progressively maturing. It is crucial to comprehend the factors influencing individuals' intention to utilize automated vehicles. This study examined user willingness to adopt automated vehicles. By incorporating age and educational background as random parameters, an ordered Probit model with random parameters was constructed to analyze the influential factors affecting respondents' adoption of automated vehicles. We devised and conducted an online questionnaire survey, yielding 2105 valid questionnaires. The findings reveal significant positive correlations between positive social trust, perceived ease of use, perceived usefulness, low levels of perceived risk, and the acceptance of automated vehicles. Additionally, our study identifies extraversion and openness as strong mediators in shaping individuals' intentions to use automated vehicles. Furthermore, prior experience with assisted driving negatively impacts people's inclination toward embracing automated vehicles. Our research also provides insights for promoting the adoption of automated vehicles: favorable media coverage and a reasonable division of responsibilities can enhance individuals' intentions to adopt this technology.


Asunto(s)
Vehículos Autónomos , Intención , Humanos , Tecnología , Viaje , China
16.
Nat Immunol ; 25(3): 496-511, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38356058

RESUMEN

Visceral adipose tissue (VAT) is an energy store and endocrine organ critical for metabolic homeostasis. Regulatory T (Treg) cells restrain inflammation to preserve VAT homeostasis and glucose tolerance. Here, we show that the VAT harbors two distinct Treg cell populations: prototypical serum stimulation 2-positive (ST2+) Treg cells that are enriched in males and a previously uncharacterized population of C-X-C motif chemokine receptor 3-positive (CXCR3+) Treg cells that are enriched in females. We show that the transcription factors GATA-binding protein 3 and peroxisome proliferator-activated receptor-γ, together with the cytokine interleukin-33, promote the differentiation of ST2+ VAT Treg cells but repress CXCR3+ Treg cells. Conversely, the differentiation of CXCR3+ Treg cells is mediated by the cytokine interferon-γ and the transcription factor T-bet, which also antagonize ST2+ Treg cells. Finally, we demonstrate that ST2+ Treg cells preserve glucose homeostasis, whereas CXCR3+ Treg cells restrain inflammation in lean VAT and prevent glucose intolerance under high-fat diet conditions. Overall, this study defines two molecularly and developmentally distinct VAT Treg cell types with unique context- and sex-specific functions.


Asunto(s)
Proteína 1 Similar al Receptor de Interleucina-1 , Linfocitos T Reguladores , Femenino , Masculino , Humanos , Grasa Intraabdominal , Citocinas , Inflamación , Glucosa
17.
Brief Bioinform ; 25(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38305456

RESUMEN

Protein structure prediction is a longstanding issue crucial for identifying new drug targets and providing a mechanistic understanding of protein functions. To enhance the progress in this field, a spectrum of computational methodologies has been cultivated. AlphaFold2 has exhibited exceptional precision in predicting wild-type protein structures, with performance exceeding that of other methods. However, predicting the structures of missense mutant proteins using AlphaFold2 remains challenging due to the intricate and substantial structural alterations caused by minor sequence variations in the mutant proteins. Molecular dynamics (MD) has been validated for precisely capturing changes in amino acid interactions attributed to protein mutations. Therefore, for the first time, a strategy entitled 'MoDAFold' was proposed to improve the accuracy and reliability of missense mutant protein structure prediction by combining AlphaFold2 with MD. Multiple case studies have confirmed the superior performance of MoDAFold compared to other methods, particularly AlphaFold2.


Asunto(s)
Aminoácidos , Simulación de Dinámica Molecular , Proteínas Mutantes , Reproducibilidad de los Resultados , Mutación , Conformación Proteica
18.
Electromagn Biol Med ; 43(1-2): 61-70, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38347683

RESUMEN

Osteoporotic osteoarthritis (OPOA) is a specific phenotype of OA with high incidence and severe cartilage damage. This study aimed to explore the protective efficacy of PEMF on the progression of OPOA and observed the effects of PEMF on PPARγ, autophagy- and apoptosis-related proteins in OPOA rats. Rats were randomly divided into three groups: control group, OPOA group, and PEMF group (n = 6). One week after surgery, the rats in PEMF group were subjected to PEMF (3.82 mT, 8 Hz, 40 min/day and 5 day/week) for 12 weeks. Results showed that PEMF retarded cartilage degeneration and bone loss, as evidenced by pathological staining image, decreased MMP-13 expression and increased bone mineral density. PEMF inhibited the serum levels of inflammatory cytokines, and the expressions of caspase-3 and caspase-8, while upregulated the expression of PPARγ. Moreover, PEMF significantly improved the autophagy disorders, represented by decrease expressions of Beclin-1, P62, and LC3B. The research demonstrates that PEMF can effectively prevent cartilage and subchondral bone destruction in OPOA rats. The potential mechanism may be related to upregulation of PPARγ, inhibition of chondrocyte apoptosis and inflammation, and improvement of autophagy disorder. PEMF therapy thus shows promising application prospects in the treatment of postmenopausal OA.


Osteoporotic osteoarthritis (OPOA) is a very common combination disease, that characterized by chronic pain, swollen joints and susceptibility to fractures. It is particularly common in postmenopausal women. At present, drug therapy is the main treatment method, but the adverse reactions are serious and can not stop the progression of the disease. PEMF is a safe physical therapy that has been shown to increase bone density, reduce pain, and improve joints mobility. In this study, we aimed to explore the protective effect and potential mechanism of PEMF on OPOA. We found that PEMF significantly inhibited the inflammatory response, ameliorated the damaged cartilage and subchondral bone in OPOA rats, that maybe related to the regulation of chondrocyte autophagy and apoptosis. This study provided a new vision for PEMF' treatment on OPOA and has positive significance for the clinical promotion of PEMF.


Asunto(s)
Apoptosis , Autofagia , Modelos Animales de Enfermedad , Osteoartritis , PPAR gamma , Ratas Sprague-Dawley , Animales , Autofagia/efectos de la radiación , PPAR gamma/metabolismo , Apoptosis/efectos de la radiación , Ratas , Osteoartritis/terapia , Osteoartritis/patología , Osteoartritis/metabolismo , Femenino , Magnetoterapia , Osteoporosis/terapia , Osteoporosis/metabolismo , Osteoporosis/patología
19.
Nucleic Acids Res ; 52(3): e13, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38059347

RESUMEN

Differential expression analysis of RNA-seq is one of the most commonly performed bioinformatics analyses. Transcript-level quantifications are inherently more uncertain than gene-level read counts because of ambiguous assignment of sequence reads to transcripts. While sequence reads can usually be assigned unambiguously to a gene, reads are very often compatible with multiple transcripts for that gene, particularly for genes with many isoforms. Software tools designed for gene-level differential expression do not perform optimally on transcript counts because the read-to-transcript ambiguity (RTA) disrupts the mean-variance relationship normally observed for gene level RNA-seq data and interferes with the efficiency of the empirical Bayes dispersion estimation procedures. The pseudoaligners kallisto and Salmon provide bootstrap samples from which quantification uncertainty can be assessed. We show that the overdispersion arising from RTA can be elegantly estimated by fitting a quasi-Poisson model to the bootstrap counts for each transcript. The technical overdispersion arising from RTA can then be divided out of the transcript counts, leading to scaled counts that can be input for analysis by established gene-level software tools with full statistical efficiency. Comprehensive simulations and test data show that an edgeR analysis of the scaled counts is more powerful and efficient than previous differential transcript expression pipelines while providing correct control of the false discovery rate. Simulations explore a wide range of scenarios including the effects of paired vs single-end reads, different read lengths and different numbers of replicates.


Asunto(s)
Perfilación de la Expresión Génica , Programas Informáticos , Perfilación de la Expresión Génica/métodos , Teorema de Bayes , Incertidumbre , Análisis de Secuencia de ARN/métodos
20.
Synth Syst Biotechnol ; 8(4): 697-707, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38025766

RESUMEN

Industrial microbes have become the core of biological manufacturing, which utilized as the cell factory for production of plenty of chemicals, fuels and medicine. However, the challenge that the extreme stress conditions exist in production is unavoidable for cell factory. Consequently, to enhance robustness of the chassis cell lays the foundation for development of bio-manufacturing. Currently, the researches on cell tolerance covered various aspects, involving reshaping regulatory network, cell membrane modification and other stress response. In fact, the strategies employed to improve cell robustness could be summarized into two directions, irrational engineering and rational engineering. In this review, the metabolic engineering technologies on enhancement of microbe tolerance to industrial conditions are summarized. Meanwhile, the novel thoughts emerged with the development of biological instruments and synthetic biology are discussed.

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